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Molecular and Cellular Biology, February 2005, p. 1339-1346, Vol. 25, No. 4
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.4.1339-1346.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Unchanged Survival Rates of 14-3-3 Knockout Mice after Inoculation with Pathological Prion Protein

Departments of Neurology,¹ Neuropathology,⁷ Psychiatry, Georg-August University Goettingen,⁸ Departments of Molecular Neurobiology,³ Neurogenetics, Max Planck Institute for Experimental Medicine, Goettingen,⁴ Department of Psychiatry, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany,⁶ Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland,² School of Biomedical and Clinical Laboratory Sciences, University of Edinburgh, Edinburgh, United Kingdom⁵

Received 5 April 2004/ Returned for modification 28 May 2004/ Accepted 4 October 2004

The diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) is based on typical clinical findings and is supported by a positive 14-3-3 Western blot of cerebrospinal fluid. However, it is not clear whether 14-3-3 indicates general neuronal damage or is of pathophysiological relevance in CJD. The fact that the 14-3-3 isoform spectrum in cerebrospinal fluid does not correspond to that found in the brain points to a regulated process. To investigate a possible role of 14-3-3 proteins in transmissible spongiform diseases, we generated a 14-3-3-deficient mutant mouse line by using a classical knockout strategy. The anatomy and cage behavior of the mutant mice were normal. Western blot analyses of brain homogenates revealed no changes in the protein expression of other 14-3-3 isoforms (, ß, , and ). Proteomic analyses of mouse brains by two-dimensional differential gel electrophoresis showed that several proteins, including growth hormone, 1-Cys peroxiredoxin, CCT-zeta, glucose-6-phosphate isomerase, GRP170 precursor, and -SNAP, were differentially expressed. Mutant and wild-type mice were inoculated either intracerebrally or intraperitoneally with the Rocky Mountain Laboratory strain of scrapie, but no differences were detected in the postinoculation survival rates. These results indicate that 14-3-3 is unlikely to play a causal role in CJD and related diseases.

* Corresponding author. Mailing address: Neurologische Klinik und Poliklinik, Georg-August-Universität Göttingen, Robert-Koch-Straße 40, 37075 Göttingen, Germany. Phone: 49-551-39-12905. Fax: 49-551-39-14449. E-mail for Markus Otto: motto{at}gwdg.de. E-mail for Petra Steinacker: psteina{at}gwdg.de.

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